A zero order release theophylline product, THEO-DUR SPRINKLE.TM., by Key Pharmaceuticals, has received widespread acceptance in the marketplace and among the medical profession as a bronchodilator. The product is a formulation of dry sustained release oral dosage micropellets in a capsule which includes upper and lower connectible parts which are easily separable from each other. The micropellets provide sustained release of theoohylline when taken by a patient and are comprised of inner seeds coated with theophylline which in turn is coated with a mixture of ethylcellulose and hydroxypropylcellulose. The oral dosage formulation is administered by separatinq the upper and lower parts of the capsule and placing the micropellets on food, the food is then eaten.
The preparation of the product is described in U.S. Pat. No. 4,587,118.
Pedersen et al, PEDIATRICS, 74 (4), 534, (Oct. 4, 1984) discovered, in a clinical study involving asthmatic children using THEO-DUR SPRINKLE theophylline micropellets, that the bioavailability and absorption pattern of the theophylline were satisfactory under fasting conditions but both absorption pattern and bioavailability were severely adversely affected by concomitant food intake. A dela y in absorption was found and the bioavailability was reduced from 91% (fasting) to 44% (P&lt;0.001). They concluded that the erratic absorption of theophylline after food intake complicates safe therapy with the preparation. This is a serious problem since the dosage form was developed for use with food by those having difficulty swallowing tablets or capsules, e.g. the elderly and children.
There is thus a need for a slow-release theophylline sprinkle composition which provides satisfactory bioavailability and absorption pattern when taken orally with food or shortly after ingestion of food, i.e., under non-fasting conditions.